Abstract
It is inconclusive nowadays for which type of congenital malformations(CMs) is increased in singleton pregnancies following after in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI) compared with those after spontaneous conception; furthermore, a complete overview is missing. We conducted a meta-analysis of cohort studies to assess the risk of specific CMs associated with IVF/ICSI singleton pregnancies. Unrestricted searches were conducted, with an end date parameter of 1 June 2017, of PubMed, Embase, Google Scholar, Cochrane Libraries, and Chinese databases. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup and sensitivity analyses were performed to explore potential heterogeneity moderators when significant heterogeneity was observed. Sixteen cohort studies with a total of 129,648 IVF/ICSI and 5,491,949 spontaneously conceived singleton births fulfilled the inclusion criteria. The IVF/ICSI singleton pregnancies had a significantly increased risk of cleft lip and/or palate (OR = 1.34 [95% CI: 1.07–1.69]; I 2 = 0%), eye, ear, face and neck (odd ratios [OR] = 1.20 [95% CI: 1.04–1.39]; I 2 = 15%), chromosomal (OR = 1.23 [95% CI: 1.07–1.40]; I 2 = 32%), respiratory (OR = 1.28 [95% CI: 1.01–1.64]; I 2 = 37%), digestive (OR = 1.46 [95% CI: 1.29–1.65]; I 2 = 0%), musculoskeletal (OR = 1.47 [95% CI: 1.25–1.72]; I 2 = 64%), urogenital (OR = 1.43 [95% CI: 1.18–1.72]; I 2 = 62%), and circulatory (OR = 1.39 [95% CI: 1.23–1.58]; I 2 = 46%) system malformations. Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. In conclusion, the IVF/ICSI singleton pregnancies are associated with higher risks for most specific CMs. Clinicians should provide appropriate information to counseling IVF/ICSI patients.
Highlights
Since the birth of the first infant conceived with in vitro fertilization (IVF) in the United Kingdom in 1978, the number of pregnancies and births resulting from assisted reproductive technologies (ART) has been increasing [1], with an estimated 200,000 ART births worldwide each year [2,3]
Finding from present study indicated that the singleton pregnancies created with ART, compared with those after spontaneous conception, experienced a significantly increased risk of 34% for cleft lip and/or palate, 20% for eye, ear, face and neck malformations, 23% for chromosomal defects, 28% for respiratory system malformations, 46% for digestive system malformations, 47% for musculoskeletal system malformations, 43% for urogenital system malformations, and 39% for circulatory system malformations, without significantly increasing the risk of nervous system malformations (P = 0.37)
Based on available data, we know that the ART singleton births have been found to be associated with an increase in congenital malformations (CMs), many studies of which are summarized in systematic reviews [13,14,15,16,17,18,19,20,21]
Summary
Since the birth of the first infant conceived with in vitro fertilization (IVF) in the United Kingdom in 1978, the number of pregnancies and births resulting from assisted reproductive technologies (ART) has been increasing [1], with an estimated 200,000 ART births worldwide each year [2,3]. A large number of cohort studies [2, 5,6,7,8,9,10,11,12] and metaanalyses [13,14,15,16,17,18,19,20] have affirmed that children conceived with ART involving IVF and/or intracytoplasmic sperm injection (ICSI) compared with those spontaneously conceived (SC) had a significantly increased risk of developing congenital malformations (CMs) It seems to be stronger for singleton births than for multiple births for the associations between ART procedures and CMs [9, 14, 20].
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